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Effect of cefoperazone alone and in combination with tobramycin on the proximal tubular membrane of the human kidney

Wirkung von Cefoperazon allein und in Kombination mit Tobramycin auf die Membran des proximalen Tubulus der Niere beim Menschen

  • Clinical Pharmacology
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Summary

The elimination of alanine-aminopeptidase (AAP), a marker enzyme of the brush border membrane of the human kidney cortex, in the urine was used to evaluate tubular damage caused by various aminoglycosides and cephalosporins, used alone or in combination, and also by cephalosporins in combination with loup diuretics. Aminoglycosides caused a dose-dependent cumulative increase in the output of AAP based on their accumulation in the tubular cell. Cephalosporins in general had no effect on tubular membranes. Cefoperazone showed a responder and a non-responder group. The combination of tobramycin with cefoperazone resulted in additive effects on the output of AAP when tobramycin was administered twice daily. The simultaneous application of cefoperazone and furosemide had no influence on the release of membrane proteins from the proximal tubule into the urine.

Zusammenfassung

Die Elimination der Alanin-Aminopeptidase (AAP) im Harn, einem Markerenzym für die Bürstensaummembran des proximalen Tubulus, wurde zur Bestimmung tubulärer Alterationen durch verschiedene Aminoglykoside, Cephalosporine und deren Kombinationen, sowie die Kombination von Cephalosporinen mit Schleifendiuretika, herangezogen. Aminoglykoside bewirkten einen dosisabhängigen Anstieg der AAP-Aktivitäten im Harn, der kumulativ verlief entsprechend der Akkumulation der Aminoglykoside in der Tubuluszelle. Im allgemeinen zeigen Cephalosporine keine Wirkungen auf die Membran des proximalen Tubulus. Bei Cefoperazon konnte eine „responder“ von einer „non-responder“ Gruppe unterschieden werden. Die Kombination von Tobramycin mit Cefoperazon führte zu additiven Effekten in der AAP-Elimination, wenn das Aminoglykosid zweimal appliziert wurde. Die gleichzeitige Gabe von Cefoperazon mit Furosemid hatte keine Wirkung auf die Ausscheidung von Membranproteinen aus dem proximalen Tubulus in den Harn.

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  1. Centre for Internal Diseases, University of Frankfurt, D-6000, Frankfurt/Main 70, W. Germany

    A. W. Mondorf

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Mondorf, A.W. Effect of cefoperazone alone and in combination with tobramycin on the proximal tubular membrane of the human kidney. Infection 9 (Suppl 1), S30–S33 (1981). https://doi.org/10.1007/BF01641035

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  • DOI: https://doi.org/10.1007/BF01641035

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